DESCRIPTION (Applicant's Description): This proposal is designed to enable Dr. Asad Bashey to spend four years gaining intense research experience and development under the mentorship of Dr. Flossie Wong-Staal at the University of California, San Diego. Dr. Bashey, who has specialized in clinical hematology/oncology and bone marrow transplantation, has had some previous experience in biomedical research at the Institute of Cancer Research in London, UK. There he acquired expertise in the molecular biology of human leukemia and signal transduction. His work was productive of several publications and a Ph.D. degree. At UCSD he has completed his clinical training and developed an interest in targeting chimeric gene products in human leukemia using ribozymes. Under the supervision of Dr. Wong-Staal, his current goals focus upon the pre-clinical development of ribozymes and RNAse P external guide sequences directed against the E2A-PBX1 and BCR-ABL chimeric transcripts in human leukemia. These ribozymes will be optimized in vitro and in cell culture and animal models of these leukemias. The most effective means of delivery and high level expression of these small RNA molecules will be analyzed. Dr. Bashey's long term goals involve the clinical application of the therapeutic modalities he is developing in the laboratory and expanding their use to other human malignancies. He will continue to explore novel therapeutic strategies which are rationally based upon an understanding of the molecular pathogenesis of malignancy. Dr. Wong-Staal's laboratory has been pioneering in the development of ribozymes for the treatment of human disease. The UCSD campus will also provide several important collaborators for this proposal and an excellent academic environment including courses and seminars for Dr. Bashey's development into an independent investigator.